Responsiveness to noradrenaline in aorta from wild-type, nitric oxide synthase-2, nitric oxide synthase-3 and α 2A/D-adrenoceptor knockout mice

Abstract

We have investigated the responsiveness of mouse aorta to noradrenaline (10 μM). In wild-type mice, noradrenaline produced an initial peak contraction (3.35±0.28 mN) and a significantly smaller plateau response (2.15±0.41 mN). The contractions were similar in aorta from nitric oxide synthase-2 (NOS-2) knockout mice. In vessels from NOS-3 knockout mice, noradrenaline contractions consisted of an early steeply rising phase with a later shallow rising phase to a maximum (10.21±0.84 mN), which was significantly greater than in wild-type and NOS-2 knockout mice, and resembled the contraction to phenylephrine (10 μM) in wild-type. In α 2A/D-adrenoceptor knockout mice, the noradrenaline maximum was significantly smaller than in NOS-3 knockout but significantly larger than in wild-type. Following N G-nitro- l-arginine methyl ester ( l-NAME, 10 μM), responses in wild-type and α 2A/D-adrenoceptor knockout were as in NOS-3 knockout mice. The α 2D-adrenoceptor antagonist BRL 44408 (2-((4,5-dihydro-1 H-imidazole-2-yl)methyl)-2,3-di-hydro-1-methyl-1 H-isoindole maleate; 1 μM) increased noradrenaline-induced contractions and the α 2-adrenoceptor agonist xylazine reduced Prostaglandin F 2α-induced contractions, in wild-type but not NOS-3 knockout. Contractions to noradrenaline in mouse aorta are modulated by NOS-3 and part of the effect involves activation of α 2A/D-adrenoceptors.